The ultimate goal of the Leukemia-Lymphoma Program is to cure and prevent leukemia and lymphoma. This problem is attacked by utilizing an interdisciplinary approach to reach specific, intermediate goals. Project I will determine the effects of neoplasia on lymphocyte function in man by examining membrane-initiated biochemical events, and the synthesis and release of lymphokines. This project will study the use of early biochemical events in the lymphocyte as a sensitive, rapid assay for cellular immunity to a variety of antigens including tumor antigens. Project II will study the role of human RNA tumor viruses in the etiology of leukemia and lymphoma by determining the presence of antibody to RNA tumor virus antigens in patients and family members as well as the actual detection of RNA viral antigens in malignant cells by immunologic means. The relationship between immunity to RNA tumor virus immunity and tumor specific immunity will be explored. The effect of radiation, chemotherapy and immunotherapy on these specific immune responses will be studied. Project III will utilize serologic and non- serologic techniques to determine whether various leukemias and lymphomas represent proliferative diseases of B or T lymphocytes. This identification will be correlated with morphology and clinical course to determine whether this classification has prognostic or therapeutic implications. These studies also will aid in the immunologic evaluation of patients prior to and during immunotherapy by quantitating the number of circulating B and T cells. Project IV will yield information regarding the nature and organization of the cell membrane particularly in regards to the glyco- and lipoprotein complexes of the cell surface. Application of these ultrastructural cytochemical and freeze etch procedures to leukemic cells and normal bone marrow cells will characterize the membrane structural changes associated with malignant cell transformation. Project V will examine the effects of immunotherapy with transfer factor on cellular immunity specific tumor immunity and clinical course of the disease in man. Project VI will study azacytidine, arabinosyl cytosine and adriamycin as well as several analogs in order to establish optimal therapeutic regimens and to identify new analogs with potent antineoplastic effects.